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High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24 h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.

The influence of orientation and temperature on fatigue short crack propagation behavior of Inconel 718 alloy was studied at both 25 °C and 650 °C by in-situ fatigue testing under scanning electron microscope. The fatigue crack growth rates (FCGR) showed evident dependence on orientation at both temperatures, following: XZ

The blood-brain barrier (BBB), comprised of brain endothelial cells with tight junctions (TJ) between them, regulates the extravasation of molecules and cells into and out of the central nervous system (CNS). Overcoming the difficulty of delivering therapeutic agents to specific regions of the brain presents a major challenge to treatment of a broad range of brain disorders. Current strategies for BBB opening are invasive, not specific, and lack precise control over the site and timing of BBB opening, which may limit their clinical translation. In the present report, we describe a novel approach based on a combination of stem cell delivery, heat-inducible gene expression and mild heating with high-intensity focused ultrasound (HIFU) under MRI guidance to remotely permeabilize BBB. The permeabilization of the BBB will be controlled with, and limited to where selected pro-inflammatory factors will be secreted secondary to HIFU activation, which is in the vicinity of the engineered stem cells and consequently both the primary and secondary disease foci. This therapeutic platform thus represents a non-invasive way for BBB opening with unprecedented spatiotemporal precision, and if properly and specifically modified, can be clinically translated to facilitate delivery of different diagnostic and therapeutic agents which can have great impact in treatment of various disease processes in the central nervous system.

Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) plays a key role in atherosclerotic plaque initiation, formation and rupture, as well as in hyperlipidemia-induced glomerular disease. Here we report a sensitive, specific and biocompatible LOX-1-targeted-USPIO for the noninvasive MR imaging of LOX-1 within carotid atherosclerotic lesions and glomerular disease in apoE-deficient mice. In vitro analysis showed the highest uptake of targeted USPIOs in only activated RAW264.7 macrophages, and in vivo MRI studies showed signal loss in carotid atherosclerotic lesions after administration of targeted USPIOs at 8 h and 24 h. These areas of signal loss were correlated with the presence of nanoparticles in the atherosclerotic lesions, and immunohistochemistry and Perl’s staining confirmed the co-localization of the LOX-1/macrophages/MMP-9 and targeted nanoparticles. Finally, additional studies suggest that this targeted probe may have potential to noninvasively image early glomerular disease. This finding may provide important methods for characterizing vulnerable atherosclerotic plaques and hyperlipidemia-induced glomerular diseases. From the Clinical Editor A functionalized USPIO-based negative contrast material was used in this study, demonstrating feasibility of sensitive MRI-based detection of atherosclerotic plaque formation in the carotid arteries and in the renal cortex, paving the way to potential future clinical applications.

In the era of medical cost containment, radiologists must continually maintain their actual and perceived value to patients, payers, and referring providers. Exploitation of current and future digital technologies may be the key to defining and promoting radiology's "brand" and assure our continued relevance in providing predictive, preventive, personalized, and participatory medicine. The Association of University of Radiologists Radiology Research Alliance Digitization of Medicine Task Force was formed to explore the opportunities and challenges of the digitization of medicine that are relevant to radiologists, which include the reporting paradigm, computational biology, and imaging informatics. In addition to discussing these opportunities and challenges, we consider how change occurs in medicine, and how change may be effected in medical imaging community. This review article is a summary of the research of the task force and hopefully can be used as a stimulus for further discussions and development of action plans by radiology leaders.

A series of polycrystalline Sr1−1.5xHoxBi2Nb2O9 (SHoBNx) (x = 0.0, 0.01, 0.03, 0.05, 0.1, 0.15, 0.2 and 0.3) samples were synthesized through solid-state reaction method, and their micro-structural, ferroelectric, dielectric and photoluminescence properties were carefully investigated. Significant enhancement of polarization and dielectric permittivity has been confirmed in SHoBNx system through ferroelectric and dielectric measurement. More importantly, the photoluminescence properties of SHoBNx system have also been explored for the first time. Sharp green emission band was observed and photoluminescence mechanism was simply discussed. It is believed that SHoBNx ferroelectric ceramics can also act as a potential blue exciting green light emission phosphor.

The term "Molecular Imaging" has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term "Systems Diagnostics" and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.

Objectives The aim of this research was to synthesize radiolabeled peptidomimetic integrin α v β 3 antagonists that selectively target integrin α v β 3 receptor and clear rapidly from the whole body. Methods Integrin α v β 3 antagonists, 4-[2-(3,4,5,6-tetrahydropyrimidine-2-ylamino)ethyloxy]benzoyl-2-( S )-aminoethylsulfonyl-amino-β-alanine (IA) and 4-[2-(3,4,5,6-tetrahydro-pyrimidin-2-ylamino)-ethyloxy]benzoyl-2-( S )-[ N -(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonylamino-β-alanine hydrochloride (IAC), a hydrophobic carbamate derivative of IA, were conjugated with 2- p -isothiocyanatobenzyl-DOTA at the amino terminus and labeled with 111 In. The 111 In labeled IA and IAC were subjected to in vitro receptor binding, biodistribution and imaging studies using nude mice bearing the receptor-positive M21 human melanoma xenografts. Results The 111 In-labeled IA (40%) and -IAC (72%) specifically bound in vitro to α v β 3 (0.8 μM) at a molar excess. This receptor binding was completely blocked by a molar excess of cold IA to α v β 3 . The higher receptor-binding affinity of the 111 In-labeled IAC was reflected in higher tumor uptake and retention: 5.6±1.4 and 4.5±0.7 %ID/g vs. 3.8±0.9 and 2.0±0.3 %ID/g for the 111 In-labeled IA at 0.33 and 2 h. The tumor uptakes were inhibited by the co-injection of 200 μg of IA, indicating that the uptake was receptor mediated. These antagonists were excreted primarily via the renal system. The 111 In activity retained in the whole body was quite comparable between the 111 In-labeled IA (24% ID) and the 111 In-labeled IAC (33% ID) at 2 h. The higher peak tumor uptake and longer retention resulted in higher tumor-to-background ratios for the 111 In-labeled IAC at 2 h with 9.7, 2.3, 0.8, 1.9, 7.1, 2.2, 0.9, 3.7 and 9.9 for blood, liver, kidney, lung, heart, stomach, intestine, bone and muscle, respectively. The imaging studies with the 111 In-labeled IAC also clearly visualized the receptor-positive tumor at 4 h. Conclusions The 111 In-labeled IAC showed an improve tumor targeting kinetics with rapid accumulation and prolonged retention in the α v β 3 receptor-positive tumor. This together with the rapid whole-body clearance pharmacokinetics warrants further studies on this IAC analog for molecular imaging of tumor-induced angiogenic vessels and various malignant human tumors expressing the receptor.

This paper presents a new way of designing bulk metallic glasses in Cu–Ti–Zr–Ni system based upon binary deep eutectic. By conventional copper mold casting method, these alloys can be quenched into single amorphous structure with the diameter ranging from 3 to 5 mm. Experimental results show that among the alloy series designed Cu 52.55 Ti 30.05 Zr 11.4 Ni 6 and Cu 53.1 Ti 31.4 Zr 9.5 Ni 6 possess the relatively higher T rg of 0.603 and 0.598, respectively, which contribute to their good glass forming ability, and Cu 52.55 Ti 30.05 Zr 11.4 Ni 6 exhibits a relatively higher T g (694 K) and Δ T x (52 K), which indicate its good thermal stability.

Optical properties of star-shaped ZnO nanostructures were studied. The temperature-dependent photoluminescence (PL) was examined up to fourth-order longitudinal optical (LO) phonon assisted emissions of free excitons and confirmed that the nature of the room temperature PL in ZnO is 1-LO phonon assisted emission of free excitons. Low threshold ultraviolet stimulated emissions (SE) were obtained for our powder samples at room temperature. Picosecond time-resolved PL measurements detected a bi-exponential decay behavior which is strongly dependent on the excitation intensity: the slow decay term decreased faster than the fast decay term as the excitation intensity increased and the emission decays were dominated by the fast one. We also found that the emission decays decreased super-linearly before the appearance of the SE. This behavior may be used to deduce the threshold of SE or lasing.

Rationale and Objectives To investigate the potential of using pulsed high-intensity focused ultrasound (HIFU) exposures to enhance the delivery, and hence therapeutic effect of liposomal doxorubicin (Doxil) in a murine breast cancer tumor model. Materials and Methods Tumors were grown in the bilateral flanks of mice using a mammary adenocarcinoma cell line. Experiments consisted of exposing one of two tumors to pulsed-HIFU, followed by tail vein injections of Doxil. Tumor growth rates were monitored, and assays carried out for doxorubicin concentration in these tumors as well as in a second (squamous cell carcinoma) tumor model and in muscle. Laser scanning confocal microscopy was used with fluorescent probes to observe both the uptake of polystyrene nanoparticles and dilation of exposed blood vessels. Additional experiments involving histologic analysis and real-time temperature measurements were performed to determine the safety of the exposures. Results Pulsed-HIFU exposures were shown to be safe, producing no apparent deleterious effects in the tumors. The exposures, however, were not found to enhance the delivery of Doxil, and consequently did not allow for lower doses for obtaining tumor regression. Imaging with a fluorescent dextran showed blood vessels to be dilated as a result of the exposures. Experiments with polystyrene nanoparticles of similar size to the liposomes showed a greater abundance to be present in the treated tumors. Conclusion Although past studies have shown the advantages of pulsed-HIFU exposures for enhancing delivery, this was not observed with the liposomes, apparently because of their inherent ability to preferentially accumulate into tumors on their own. Potential mechanisms for enhanced uptake of non-liposomal nanoparticles are discussed.

Molecular imaging (MI) in the broader sense is the characterization and measurement of biologic processes at the cellular and molecular level to elucidate various disease processes (1,2); however, for radiologists, MI can be considered as the evolution of clinical diagnostic imaging techniques toward a more specific characterization of disease processes and gradually toward a personalized level (3). As genetic engineering progresses, MI may also be a way of following this process in vivo for improved presymptomatic disease detection and for providing tools to follow progression of the disease or response to various therapies (4). Since the inception of MI, its utility and development in clinical diagnosis and therapy monitoring has continued to evolve at a rapid pace (5–7). Just as visual observations of morphologic tissue changes on conventional clinical imaging techniques gave way to the physiological examinations of inner organs through the practice of radiology, novel MI applications will further develop the clinician’s ability to detect disease at earlier stages to more accurately follow the patient through the disease process. Further advances in clinical MI seek to extend disease characterization by harnessing rapid advancements of existing imaging technologies with the simultaneous evolutions in the field of molecular biology for the study of disease processes (8–12). With current technology, direct in vivo observation of molecules is beyond the scope of most noninvasive imaging technologies. However, many diagnostic studies can extend by inference down to the molecular level those events that may be used for a better

Imagine administering a chemical in a live animal, looking at its interactions at molecular and cellular level, and identifying in real time various physiologic and pathologic conditions. To many people, this idea may feel like science fiction. Novel chemicals that are in research and development should help to make such a scenario a research and clinical reality in many applications. These chemicals under investigation that are used to probe molecular function at the molecular and cellular level in vitro, ex vivo, and or in vivo are called molecular probes (MPs). They provide high sensitivity for imaging minute molecular systems such as receptors, enzymes, and transporters. MPs are classified according to the imaging techniques with which they are used, and the selection of MPs is dependent on the type of imaging modality. MPs can be radioactive or nonradioactive and be designed to image endogenous or exogenous genes, messenger ribonucleic acid transcripts, or the expressed proteins (receptors, enzymes, and transporters). MPs that target proteins have been a major focus because they are expressed in large numbers (thousands to millions of copies per cell) and can allow the accumulation of the MPs in a specific site or tissue and thus can produce good signal-to-noise ratio. Also, protein expression is the ultimate result of genetic processing and hence imaging protein expression is a good choice. Imaging is mainly used for assessing morphology noninvasively. However, much excitement has been generated regarding the potential of using MPs to image specific

Building on genomics and the success of the Human Genome Project (HGP), this article will introduce the field of proteomics and the potential it has for making substantial contributions to biomedical and clinical research. Information gained from the HGP has given us a detailed “blueprint” of the 25,000–30,000 genes contained within the human genome. Using these data, significant advances have been made in our understanding of genes and their regulation. However, the downstream effectors of genes, namely proteins, are thought to be more interesting and to hold the most clinical significance. Proteins are involved in nearly all biologic activities, are central to most disease processes, and are the targets of the vast majority of drugs. Proteomics has the potential to allow for the much broader understanding of how proteins function together at the molecular level, which hopefully will translate into a better understanding of disease processes and improved clinical therapies. Proteomics is defined as the study of all the proteins within an organism. An all-encompassing term, proteomics attempts to describe the identity, quantity, three-dimensional structure, interactions, posttranslational modifications, and functions of all the proteins expressed within a particular location at any one point in time. Unlike the genomic sequence, which is essentially static and identical within all cells, the proteome is unique to each cell and constantly changes with each physiologic and pathologic process. The emerging field of proteomics seeks to make sense of the variation in protein abundance and ac

This article along with the first 2 in this series (4,12) completes the discussion on the key molecules and process inside the cell namely, DNA, RNA, and proteins. These 3 articles provide a very basic foundation for understanding molecular biology concepts and summarize some of the work of numerous scientists over the past century. We understand these processes far better now than we did in the past, but clearly this knowledge is by no means complete and a number of basic scientists are working hard to elucidate and understand the fundamental mechanisms that operate within a cell. Genes and gene products work with each other in complex, interconnected pathways, and in perfect harmony to make a functional cell, tissue, and an organism as a whole. There is a lot of cross-talk that happens between different proteins that interact with various other proteins, DNA, and RNA to establish pathways, networks, and molecular systems as a team working to perfection. The past 15 years have seen the rapid development of systems biology approaches. We live in an era that emphasizes multi-disciplinary, cross-functional teams to perform science rather than individual researchers working on the bench on a very specific problem. Global approaches have become more common and the amount of data generated must be managed by trained bioinformatics personnel and large computers. In our subsequent articles, we will discuss these global approaches and the areas of genomics, functional genomics, and proteomics that have revolutionized the way we perform science.

Chemical sensitivity of silicon nanowires bundles has been studied. Upon exposure to ammonia gas and water vapor, the electrical resistance of the HF-etched relative to non-etched silicon nanowires sample is found to dramatically decrease even at room temperature. This phenomenon serves as the basis for a new kind of sensor based on silicon nanowires. The sensor, made by a bundle of etched silicon nanowires, is simple and exhibits a fast response, high sensitivity and reversibility. The interactions between gas molecules and silicon nanowires, as well as the effect of silicon oxide sheath on the sensitivity and the mechanisms of gas sensing with silicon nanowires are discussed.

Ultrafine and uniform silicon nanowires (SiNWs), with a Si crystalline core of 1–5 nm (average 3 nm) in diameter and a SiO2 outer layer of 10–20 nm thick, were synthesized by the oxide-assisted growth method via the disproportionation of thermally evaporated SiO using zeolite as a template/precursor. From transmission and secondary electron microscopic characterizations, we deduced that the zeolite acted to limit the lateral growth of the Si crystalline core and supply the excess oxide to form the thick oxide outer layer. The ultrafine SiNWs exhibited strong photoluminescence that peaked at 720 nm.

Growth of silicon nanowires (SiNWs) by thermal evaporation of SiO in a closed system was studied. The yield of SiNWs obtained in the present closed system was much higher than that from the previous open systems. As the ambient pressure increased, the yield of SiNWs decreased and the diameter of the SiNWs increased, but the surface of the SiNWs was roughened. Transmission electron microscopic examination showed that the originally smooth surface of SiNWs was roughened by the formation of Si nano-particles. The implication of these results on the growth mechanism of the SiNWs is discussed.

Ternary PbSnSe layers with various Sn contents were grown by LPE on Si(1 0 0) substrates prepared with MBE-grown PbSe/BaF 2 /CaF 2 buffer layers. LPE growth initiation temperatures were varied from 380 to 475°C by changing the chalcogen concentration in the LPE growth solution. PbSe/PbSnSe double layers were also grown using the same procedure. Crack densities and residual strain values in the epilayers were measured by optical Nomarski microscopy and high-resolution X-ray diffraction (HRXRD). Crack densities in Pb 0.91 Sn 0.09 Se layers decreased from 93 to 33 cracks/cm when the growth temperature was increased from 430 to 475°C. Crystalline quality, as indicated by HRXRD FWHM reduction from 522 to 442 arcsec, also improved with this increase in growth initiation temperature. These results show that IV–VI semiconductor layers grown at higher temperatures are more able to plastically deform when subjected to cooling strain caused by thermal expansion mismatch with the Si substrate. Activation of a strain-relieving higher-order dislocation glide mechanism is a likely explanation for this observation.

In the past few years, tremendous advances have been made in the fields of magnetic resonance imaging, computed tomography and ultrasonography. These include the development of novel contrast agents and new approaches to image acquisition and processing. This review provides an overview of the state-of-the-art of imaging investigation of focal hepatic lesions and highlights some of the most exciting emerging technologies.

Rationale and Objectives. The authors attempted to determine whether the T2 relaxation time of superior mesenteric vein (SMV) blood would decrease in patients with chronic mesenteric ischemia after a meal. Materials and Methods. Thirty-two patients without chronic mesenteric ischemia and eight patients with symptomatic chronic mesenteric ischemia underwent magnetic resonance (MR) imaging. All examinations were performed with a 1.5-T unit, a modified Carr-Purcell-Meiboom-Gill sequence, final section-selective pulse of 180°, and spiral readout gradients. Measurements of SMV blood T2 were obtained after at least 6 hours of fasting and 15 and 35 minutes after ingestion of 240 mL of a liquid nutritional supplement. Maximal change of the SMV blood T2 was expressed as a percentage of the fasting T2 in all patients. Results. In control patients, SMV blood T2 increased postprandially by 9.4% ± 1.3 (95% confidence level; range, 6.8%–11.9%) (data range, −7.3% to 25.6%) compared with fasting T2. In symptomatic patients, SMV blood T2 decreased postprandially by 15.8% ± 2.2 (95% confidence level; range, −20.1% to −10.7%) (data range, −7.9% to −25.3%). The difference between the two groups was statistically significant ( P t test). Conclusion. Measurement of SMV blood T2 is a promising test for chronic mesenteric ischemia diagnosis. Therefore, conversion of T2 measurements to estimate oxygen saturation may not be necessary for all cases of this clinical indication.

Partially ordered Sm 2 Fe 17 , closer to the SmFe 7 structure, formed upon melt spinning of Sm 11 Fe 89 . A strong dependence of grain size on the wheel speed was also observed, with wheel speeds less than 40 m/s generating grain sizes above the single domain limit for Sm 2 Fe 17 N x . The addition of Ti and C resulted in an order of magnitude grain refinement compared to the binary alloys. The Ti and C also effectively inhibited grain growth during annealing. The nitrided Sm–Fe–Ti–C alloys also displayed a rapid decrease in coercivity with decreasing grain size, which was attributed to increased exchange interactions.

Using contrast-enhanced MR angiography, cine phase contrast MR imaging, and flow-independent T2 measurements, MR imaging can provide both morphologic information about the degree of stenosis of the mesenteric vessels and quantitative functional information about blood flow and blood oxygen saturation in these vessels. The combination of these techniques can potentially revolutionize the diagnosis and post-treatment assessments of both acute and chronic mesenteric occlusive disease.

Rationale and Objectives. The authors tested the hypothesis that changes in oxygen saturation (%HbO 2 ) in the superior mesenteric vein (SMV), as measured with in vivo magnetic resonance (MR) oximetry, correlate with the degree of acute superior mesenteric artery (SMA) flow reduction. Methods. Ten mongrel dogs were studied. A catheter was inserted into the SMV, and a perivascular ultrasonic flow probe and an adjustable mechanical occluder were placed around the SMA. MR oximetry was carried out at the resting state and after the SMA was constricted to predetermined levels (0%–75% of initial flow). In seven dogs, SMV blood samples were obtained immediately before and after each MR measurement; %HbO 2 was measured simultaneously by using an oximeter. With linear regression analysis, the SMV %HbO 2 measurements obtained at MR imaging were compared with those obtained at oximetry. With a logistic model, MR imaging changes in SMV %HbO 2 were compared with the degree of SMA flow reduction. Results. SMV %HbO 2 measurements obtained with MR imaging correlated well with those obtained with oximetry ( r = .97). Changes in SMV %HbO 2 measured at MR imaging also correlated well with the degree of SMA flow reduction, as determined with a logistic model ( P = .01). Conclusion. Noninvasive in vivo MR measurements of SMV %HbO 2 can be used to determine the degree of acute SMA flow reduction with a high degree of accuracy in a canine model.

Preoperative assessment of orthotopic liver transplantation candidates requires definition of both the anatomy and metabolic function of the native liver. Current evaluation techniques combine computed tomographic scanning, duplex ultrasonography with blood chemistry analysis, and physical stigmata of end-stage liver disease. Recently, magnetic resonance imaging (MRI) has emerged as an alternative method for delineation of hepatic and portal venous anatomy. In addition, MRI accurately measures hepatic volume and portal venous blood flow.To examine the role of MRI-derived indexes of hepatic hemodynamics in the preoperative assessment of liver function, 39 consecutive liver transplantation candidates were studied in a prospective manner. Liver function (aspartate aminotransferase), alanine aminotransferase, alkaline phosphatase, total bilirubin, and albumin levels), hematologic indexes (complete blood cell count, prothrombin time), and Child's classification were determined at the time of evaluation. Axial breath-held multiplanar spoiled-gradient echo MRI measured hepatic volume, whereas a cine phase-contrast sequence perpendicular to the portal vein measured flow.Hepatic index, defined as hepatic mass corrected for body surface area, was found to correlate with prothrombin time (p0.04) and platelet count (p0.03) by multivariate regression analysis. Portal flow index (PFI), defined as portal flow corrected for hepatic mass), was associated with aspartate aminotransferase (p0.02), alanine aminotransferase (p0.04), and albumin (p0.03) by multivariate regression analysis. In addition, PFI was closely correlated with the patients' functional status as determined by Child's classification system. Increasing values of PFI were associated with declining hepatic functional reserve. Child's class A patients had a mean PFI that was two times less than that of Child's class B patients (0.26 +/- 0.04 versus 0.04 +/- 0.06 ml/min/gm; p0.02) and five times less than that of Child's class C patients (0.26 +/- 0.04 versus 1.05 +/- 0.14 ml/min/gm; p0.001). Similarly, the mean PFI associated with Child's class B was two times less than that of Child's class C (0.46 +/- 0.06 versus 1.05 +/- 0.14 ml/min/gm; p0.01). These data show that MRI-derived indexes of portal hemodynamics and hepatic mass (1) correlate well with biochemical indexes of hepatic dysfunction and (2) serve as anatomic and hemodynamic correlates to Child's functional classification.We conclude that MRI may serve to noninvasively delineate preoperative hepatic vascular anatomy and metabolic dysfunction in candidates undergoing examination for liver transplantation.

Cancer research has achieved dramatic advances in recent years with modern techniques and aroused extensive efforts to discover effective therapeutic drugs. As complement to time and resource intensive traditional drug development methods, application of computational models for drug pharmacokinetics and pharmacodynamics research has become increasingly popular because of its high efficiency and flexibility. Our work provides a well-designed integrated mechanistic model for developing cancer drugs by incorporating new techniques like PET, CT, and intravital microscopy. This model studies drug distribution and therapeutic effects from a systematic viewpoint at three different yet highly related levels. Firstly, a macro-scale model was established to study time course drug distributions in different organs especially in blood which circulates in whole body and delivers drug to targeted tumor. At the intratumoral level, a coupled 3D tumor growth and angiogenesis model was proposed to elaborately simulate neovasculature formation and calculate regional variations in drug distribution inside solid tumor. The third part focuses on how regional variations in drug distribution affect tumor cell death/proliferation rate by linking therapeutic response to intracellular signaling pathway blockade or alteration, which provides us a high-resolution overview of drug action in the targeted tumor cell. Hence, the first two modules which target the organ level and intratumoral microenvironment are directly coupled to pharmacokinetics analysis which is linked to the last component of the model that analyzes the pharmacodynamic effects at the cellular level. Experimental data for calibrating computational model, like drug distribution, tumor vasculature, drug penetration rate etc., were measured using PET, CT, and high resolution intravital microscopy. We perform simulations to investigate the delivery efficiency and drug efficacy of free drug and nanotherapeutics. Our model successfully predicted optimal drug property and therapy strategy. Finally, model effectiveness was validated by in vivo experimental data.

Polyaniline films of different thickness were formed on Pt and Au electrodes. In-situ epr spectra at different applied potentials in various pH media were reported in order to clarify the conducting mechanism. The results indicate that upon electrochemical doping of polyaniline, an equilibrium between polaron and bipolaron occurs. The thicker the film, the more stable the polaron. The more acidic the medium, the more stable the polaron. The stability of the polaron of polyaniline formed on Pt is better than those formed on Au electrode. A small epr spin density maximum appear before the major spin density maximum on the plot of spin density versus applied potential of polyaniline formed on Pt electrode. This phenomenon may result from polarons in different environments.

An unstructured-grid, finite-volume method has been developed for simulating the inviscid flow over spacecrafts of realistic configuration. The grid generation is accomplished by a new technique on the basis of the advancing-front concept. This simple technique is shown to be equally as powerful for a complex multibody as for a single vehicle. Second- or third-order accuracy is obtained via an innovative interpolation procedure similar to the conventional MUSCL approach. This method has been applied to the Shuttle orbiter and a representative Shuttle launch vehicle consisting of the orbiter, the external tank, and the solid rocket boosters. A comparison is discussed between the present results and other results obtained from structured- and unstructured-grid methods.

In order to determine the normal variations of pelvic fat distribution, 25 men and 25 women normal pelvic computer tomography (CT) scans were reviewed. No distinct fat planes were demonstrated between the prostate and pelvic side walls, bladder and seminal vesicles, and prostate and rectum in 69%, 81%, and 86% of the men patients, respectively. Similarly, there were no distinct fat planes between the uterus and pelvic side walls, and uterus and rectum in 86% and 96% of the women patients, respectively. We conclude that there are no distinct fat planes around pelvic organs in the majority of normal people and this may be a major source of error in the CT staging of pelvic tumors.

The combination of a paramagnetic agent with an oil emulsion can uniformly enhance the small bowel. We discovered that the entire small bowel becomes homogeneously brighter than its surroundings when imaged with all commonly utilized pulse sequences. We have tried various combinations of ferric ammonium citrate, ferrous sulfate, gadolinium-DPTA and corn oil, olive oil and peanut oil. All paramagnetic oil emulsions tested were uniformly distributed throughout the small bowel, but the enhancement effect is much stronger with the ferric ammonium citrate and gadolinium-DPTA oil emulsions. We have also developed a mixture of Geritol, corn oil, ice cream and milk, which uniformly coats the small bowel wall, has good enhancement effect, tastes good, and is nutritious. With this dietary contrast, retroperitoneal structures including the pancreas can be well delineated. We conclude that the combination of a paramagnetic agent with an oil emulsion can work as a safe and effective magnetic resonance imaging (MRI) oral contrast agent with high patient acceptance.

Stem cell therapy has captured the fascination of the lay press for many years and has been touted as the potential cure for many diseases including heart disease, stroke, neurodegenerative disease, diabetes, and even cancer. It has been 6 years since California voters said yes to Proposition 71 and more than $1 billion of research funding has been distributed from this initiative alone. Many would argue that the progress so far has been steady but has not come close to matching the hype this area of research has received. This is mainly because important aspects of stem cell biology such as the factors governing survival, migration, differentiation, and integration are still not fully understood (1). The ability to track stem cells real time after transplantation noninvasively in vivo can definitely help to increase our knowledge base and shed light on how to refine our approaches in clinical stem cell therapy (1,2). The imaging methods that have been used for stem cell tracking to date can be broadly divided into two main groups: direct labeling and transgene imaging. Direct labeling of stem cells have been done with magnetic resonance (MR) contrast agents such as iron oxide particles, fluorescent imaging agents such as quantum dots, and radionuclides such as In-oxine (1–3). The major advantage of direct labeling methods is that it is relatively easy to do and some of the methods such as In-oxine labeling have been used in clinical applications already. Some of the shortcomings of the direct labeling approach stem from the fact that the detected signals come from the labels and it is impossible to know whether the labels are still inside the stem cells in vivo when the imaging experiment is performed. In addition, direct labeling also does not provide any direct information about the biologic state of the stem cells. For example, it has been shown that iron oxide labeling fails to distinguish dead from living transplanted cells in the infracted heart (4). Transgene imaging methods require cloning into the stem cells a reporter gene such as luciferase for bioluminescence imaging (BLI) or herpes simplex virus thymidine kinase (HSV1-tk) for positron emission tomography (PET). For imaging experiments, a reporter probe is injected such as luciferin for BLI or 9(4(F)fluoro-3(hydroxymethyl)butyl)guanine ((F)FHBG)

imaging data with a bolus injection of a small molecular weight MR contrast agent, gadodiamide. These measurements were then correlated with two in vitro tissue analysis parameters—tumor histologic grade and immunohistologically assessed mitotic activity by using MIB-1 immunohistochemical labeling. With only four parameters in the study, there are already 12 different one-to-one correlations that can be examined. The results of these correlations are interesting but also somewhat confusing. fBV did not correlate with any of the other parameters. The strongest correlations were between k and tumor grade (r 0.73) and between k and MIB-1 index (r 0.84). On the other hand, the correlation between tumor grade and MIB-1 index was not very high (r 0.63). In addition, k was found to be more reliable than the MIB-1 labeling index in differentiating grade 2 from grade 3 tumors.

An implicit finite-difference method is developed to integrate the parabolic Navier-Stokes equations along the main direction for flow over a finite-width plate at 0 and 10° angles of attack. This method utilizes the fractional steps (splitting) technique to seek the solution from a sequence of two-dimensional difference equations. A new linearization algorithm is devised to facilitate the calculation of Jacobian matrices in a Taylor series expansion and to perform successive iterations until the conservative-law equation is recovered. Both backward and centered implicit schemes are used in the splitting technique and the results are compared. Available numerical solutions and experimental data obtained at low-Reynolds-number conditions are also used for comparison. The backward implicit method provides a more successful solution, which ranges from the merged-layer to the strong-interaction regimes. The computed flowfield shows a shear layer around the side edge and small region of reversed lateral flow on the lee side of the plate at an angle of attack.

In a prospective study, 10 patients with well-documented osteoarthritis (O.A.) of the hips were imaged using spin-echo pulse sequences (TR = 0.5 to 1.5 s and TE = 28 to 60 ms). After analyzing the changes observed, an MR grading system for assessing severity of O.A. in the hips was developed. Using this grading system and an established grading system for osteoarthritis using roentgenograms (both systems use grades 0-4), two radiologists independently graded the MR studies and plain films separately, twice. The roentgenogram grading system was more accurate in predicting symptoms in the more severe cases, whereas the MR grading system was slightly more useful in the less severe cases. Our results show that MR can demonstrate a spectrum of changes of O.A. in the hips. Its ability to directly image articular cartilage makes it a powerful research and clinical tool.

This article discusses the most important benign liver tumors, both in adult and pediatric patients. A pathologic discussion of each neoplasm is included to provide a basis for understanding the radiologic-pathologic correlation that is used throughout the monograph. The benign liver tumors are presented according to their frequency. Therefore, hemangioma, the most common primary benign liver neoplasm, is discussed first, followed by focal nodular hyperplasia, hepatocellular adenoma, and the benign primary pediatric tumors—infantile hemangioendothelioma and mesenchymal hamartoma. Finally, a brief discussion of nodular regenerative hyperplasia and other rare hepatic masses is included. Bile duct cyst (simple, non-parasitic cyst of the liver) is not included since it is not a neoplasm. Likewise, cystadenoma is not discussed since it originates from the biliary duct cell and is appropriately included in the biliary neoplasms category.